Enormous quantities of over-the-counter drugs, cosmetics and packaged food products are produced each year for sale in sealed, shelf-stable containers. A small fraction of this production although manufactured properly fails to reach the consumer intact due to tampering or oxidative degradation. Manufacturers faced with preventing tampering have reacted by adopting a number of simple methods for providing tamper evidence to consumers and merchants. Methods commonly employed include the use of innerseals, vacuum indicators, shrinkwrap bands, film overwraps, breakaway cap rings, and other physical indicators of package integrity. Many of these methods suffer from one or more weaknesses making them vulnerable to failure at the hands of a determined individual or through lack of consumer awareness.
A number of colorimetric package integrity sensors have been reported which are designed to show a color change after a package seal is broken and the contents exposed to the atmosphere. Factors used to cause such color changes have included moisture, loss of headspace gas, and atmospheric oxygen. Of these factors, only oxygen appears to be a relatively constant indicator since it is present at about 21% of the earth's atmosphere. Thus it has been used as a basis for colorimetric reactions in package integrity testing.
For instance, Perlman et al. in U.S. Pat. No. 4,526,752 teaches the use of redox indicator dyes, i.e. methylene blue reduced to their colorless leuco forms, as oxygen indicators for the detection of tampering. The decolorized form of methylene blue turns blue very rapidly in the presence of or after exposure to oxygen. Perlman et al. teaches that the development of color, which is caused by an influx of oxygen after the package seal is broken, may be reversed when a reducing agent is present and the package is returned to an oxygen-free atmosphere. Moreover, the presence of reducing agents in the product contained in the package can adversely effect the shelf stability of the indicator and can interfere with designed operation of the system.
A similar system using redox indicator dyes such as methylene blue is disclosed in Yoshikawa et al. in U.S. Pat. Nos. 4,169,811 and 4,349,509.
Food, drug, and cosmetic systems typically contain varying amounts of common reducing agents such as glucose, fructose, maltose, lactose, sodium or zinc dithionite, ferrous sulfate, ferrous chloride, ferrous ammonium sulfate, ferrous oxalate, ferrous lactate, iron sulfide, ascorbic acid, sodium ascorbate, stannous chloride, and numerous other compounds. These reducing agents are prone to causing interference in the critical reaction leading to the formation of the colored dye products from colorless leuco-form redox compounds. Alternatively, the reducing agents in the product could cause the colored dye to revert to its colorless leuco form even after exposure to oxygen, thereby yielding false negative results. Thus, a major limitation to the use of the Perlman et al. and Yoshikawa et al. sensors is that they can not be used with those packaged products which contain reducing agents. This effectively precludes their use with most products derived from natural sources, many vitamin preparations, and some cosmetics.
Another serious limitation of the redox systems is that the conversion from leuco to color is extremely sensitive to oxygen. Thus, the reaction occurs so quickly that the sensor must be prepared, incorporated into the package, and the package sealed under completely anaerobic conditions. As a result production of packages incorporating the leuco dye sensors is inconvenient, costly, complicated, and is limited to "batch" operations characterized by low speed and efficiency.
Other sensors have been based upon causing a color change. For instance, U.S. Pat. No. 3,899,295 describes a sensor wherein a pH indicator is placed in an environment filled with an acidic or basis gas, e.g. carbon dioxide or ammonia. This indicator requires the use of reactive gases which are known to interact and combine with many components of food, drug, and cosmetic systems. As such, the sensor can affect the nutritional, sensory, and esthetic properties of materials packaged with it via chemical reaction. Another colorimetric sensor is a time-temperature sensor Lifelines.RTM. of Allied Chemical which allows a user to estimate the total heat exposure load on the sensor and attached sample. The product is composed of a monomer that polymerizes in response to heat. Also Fisher Scientific markets an indicating silica gel useful in gauging the extent to which a dry material has become hydrated over time. Also Metrohm of Switzerland has a sensor to evaluate the development of rancidity in fats and oils while in use. While the sensor works upon an oxidation system, it does not use a colorimetric system and is not useful to determine integrity of sealed packages.
It is accordingly an object of the present invention to produce a visual indicator system to readily determine loss of product integrity of an apparently sealed package. It is a further object to produce a colorimetric test having an irreversible dramatic color change. It is a still further object to produce a sensor which may be prepared aerobically and then inserted into an anaerobic environment for use. It is a still further object to produce a sensor which is unaffected by the presence of reducing agents such as are routinely incorporated in many, many commercial products. It is a still further object to produce a test which is sufficiently sensitive to show evidence of tampering within about 1 to 8 hours, but is also sufficiently insensitive that it may be prepared in an aerobic environment and then transferred into an anaerobic environment for use. It is a still further object to produce a sensor in the form of a machine-readable universal bar code which will become unreadable after exposure of it to oxygen. These and other objects will be apparent from the ensuing description.
These and other objects of the present invention are obtained by means of a colorimetric indicator system which becomes operative in the presence of oxygen and comprises a color indicator in combination with one or more oxygen-sensitive compounds which upon exposure to oxygen will cause the color indicator to change color but which is unaffected by contact with reducing agents. The presence of oxygen produces a color change in the indicator, while the absence of oxygen precludes such a change. The system is completely functional both in the presence or absence of reducing agents in the products being protected.